It meant a 14th place finish for North End from a campaign which just a few weeks ago had looked like being a play-off push.
They rarely raised a gallop in West London, their performance lacklustre at times, especially in the second half.
Brentford's opener came in the fifth minute of first-half stoppage-time - 13 minutes needed to be added on by referee James Linington after Bees defender Julian Jeanvier suffered a head injury in the first 30 seconds of the contest.
Jeanvier was on the ground for 10 minutes before he was stretchered off, then there was a shorter delay later in the first half when a stretcher was needed when a fan was taken ill.
Ezri Konsa fired the Bees ahead after loose defending at a corner, a lead which Neal Maupay doubled nine minutes into the second half.
Substitute Marcus Forss completed the scoring in the 83rd minute, putting the cap on such a disappointing afternoon for Alex Neil's men.
North End's starting XI was unchanged from the one which drew against Sheffield Wednesday, with Adam O'Reilly replacing Jack Baxter on the bench.
The game was less than a minute old when Jeanvier clashed heads with Jayden Stockley as they challenged for a ball into the box.
There followed a stoppage of more than 10 minutes when he was attended to on the pitch, put in neck brace and stretchered off.
When play resumed it was Brentford in the ascendancy with them looking the more threatening save for a short spell midway through the half.
Sergi Canos hit a shot straight at Connor Ripley, then the North End keeper almost gifted the Bees a sight of goal.
Taking a back pass from Ben Davies, he tried to side-step Maupay who had moved to close him down.
Maupay managed to get the ball off him briefly, Ripley needing to dive at his feet to take the ball off the striker's toes.
North End's best chance of the first half was a 22nd minute shot from Callum Robinson, one which keeper Luke Danies pushed behind at the near post.
Luka Racic's shot after a corner had dropped to him, was deflected behind by Darnell Fisher, then a great Brentford move across the pitch on the counter attack ended with Rico Henry blasting wide of the target.
Ripley dived to tip away Ollie Watkins' shot after he had cut inside from the left channel, that a warning sign that the bees were working up a head of steam.
Unfortunately, Preston couldn't see it through until half-time, conceding in the fifth minute of added-on time.
They made a real hash of dealing with a corner, having two or three attempts to clear their lines, the ball put back into the middle for Konsa to shoot home from six yards.
Robinson and Alan Browne both put shots over the bar from Stockley lay-offs as North End woke-up somewhat in an attacking sense towards the end of stoppage-time.
Lukas Nmecha replaced Stockley at the interval as North End went for more pace up front rather than the more direct approach.
Brentford scored their second goal in the 54th minute, the defending once again poor.
Canos' cross from the right picked-out Maupay who had space to lift a right-foot finish into the net from 10 yards.
Paul Gallagher drove a shot too high from 25 yards, while substitute Louis Moult spun and sent a low drive wide - the assistant's flag going up for offside against the striker.
Ripley made another good save in the 76th minute to tip away Maupay's volley from the right hand side of the box, with Davies scrambling the loose ball clear beyond the far post.
The home side got a third goal seven minute to wrap-up victory, not that the outcome had looked in any doubt.
Forss had only been on the pitch a short time when he was given the space to move towards the box and hit a daisy-cutter into the bottom corner of the net past Ripley who didn't move.
Brentford: Daniels, Dalsgaard, Konsa, Racic, Jeanvier (Odubajo 12), Marcondes, Dasilva, Henry, Watkins (Oksansen 77), Canos (Forss 77), Maupay. Subs (not used): Ogbene, Zamburek, Archibald, Gunnarsson.
PNE: Ripley, Rafferty, Storey, Davies, Fisher, Gallagher, Johnson, Maguire (Ginnelly 75), Browne, Robinson (Moult 60), Stockley (Nmecha 46). Subs (not used): Earl, Huntington, O'Reilly, Rudd.
Referee: James Linington (Isle of Wight)
Attendance: 11,289 (812 PNE)